Hospitalized Patients with Delirium and 28-Day Unplanned Hospital Readmissions: A Longitudinal Retrospective Cohort Study.

OBJECTIVE: To establish the predictors of 28-day unplanned hospital readmissions (28D-UHR) in older adults (aged >65 years) with delirium during index hospital admission. DESIGN: Retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: 1634 patients (aged >65 years) admitted to a Melbourne quaternary hospital with delirium during index admission. METHODS: Delirium during hospital admission was defined by the inclusion of one of the following International Classification of Diseases, Tenth Revision, codes F05.0, F05.1, F05.8, or F05.9 in the hospital medical discharge summary. Descriptive statistics were obtained for baseline characteristics. Multivariate logistic regression model was developed to assess predictors of 28D-UHR. RESULTS: A total of 1634 patients with delirium during their inpatient admission were included, with 9.8% (160 patients) incidence of 28D-UHR. For patients who were readmitted, a shorter length of stay [odds ratio (OR) 0.98, 95% CI 0.96-0.99], higher number of medications on discharge from index admission (OR 1.10, 95% CI 1.06-1.14), and residing in a nursing home preadmission (OR 1.35, 95% CI 1.04-1.75) were associated with 28D-UHR. CONCLUSIONS AND IMPLICATIONS: This study found that nursing home residence pre index admission, shorter length of stay (LOS), and polypharmacy were predictors of 28D-UHR. Further research into strategies to minimize 28D-UHR is required. Exploration of predischarge pharmacy-driven deprescribing programs and hospital-based postdischarge support for nursing home staff are important areas for future intervention.

Impact of long-term vs. short-term and single day vs. single dose of antibiotic prophylaxis in reducing infection rates after orthognathic surgery: a systematic review and meta-analysis.

BACKGROUND: This review was designed to examine the effect of long-term (≥2 days) vs. short-term (1 day) and single-day vs. single preoperative doses of antibiotic prophylaxis on surgical site infection (SSI) rates after orthognathic surgery. MATERIAL AND METHODS: PubMed, Web of Science, Embase, and Scopus were searched for randomized controlled trials (RCTs) without any date or language restriction till 1st September 2023. SSI rates were pooled to generate risk ratio (RR). RESULTS: Eight RCTs comparing long-term vs. short-term and three RCTs comparing single day vs. single preoperative dose of antibiotic prophylaxis were included. Meta-analysis showed that the use of long-term antibiotic prophylaxis significantly reduced the risk of SSI after orthognathic surgery as compared to short-term antibiotics [RR:0.42 (95% CI: 0.23, 0.76) I2=0%]. Meta-analysis also noted that patients receiving a single day of antibiotic prophylaxis had significantly reduced risk of SSI as compared to those receiving only a preoperative single dose of antibiotics [RR:0.28 (95%: 0.09, 0.82) I2=0%]. CONCLUSIONS: Evidence from a limited number of RCTs with moderate to high risk of bias shows that two to seven days of long-term antibiotic prophylaxis reduces the risk of SSI as compared to single-day antibiotic therapy. Also, a single day of antibiotics may be more beneficial than a single pre-operative dose of antibiotic.

Development and multicenter validation of a novel radiomics-based model for identifying eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Reliable noninvasive methods are needed to identify endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) to facilitate personalized therapy. Previous computed tomography (CT) scoring system has limited and inconsistent performance in identifying eosinophilic CRSwNP. We aimed to develop and validate a radiomics-based model to identify eosinophilic CRSwNP. METHODS: Surgical patients with CRSwNP were recruited from Tongji Hospital and randomly divided into training (n = 232) and internal validation cohort (n = 61). Patients from two additional hospitals served as external validation cohort-1 (n = 84) and cohort-2 (n = 54), respectively. Data were collected from October 2013 to May 2021. Eosinophilic CRSwNP was determined by histological criterion. The least absolute shrinkage and selection operator and the logistic regression (LR) algorithm were used to develop a radiomics model. Univariate and multivariate LR were employed to build models based on CT scores, clinical characteristics, and the combination of radiological and clinical characteristics. Model performance was evaluated by assessing discrimination, calibration, and clinical utility. RESULTS: The radiomics model based on 10 radiomic features achieved an area under the curve (AUC) of 0.815 in the training cohort, significantly better than the CT score model based on ethmoid-to-maxillary sinus score ratio with an AUC of 0.655. The combination of radiomic features and blood eosinophil count had a further improved performance, achieving an AUC of 0.903. The performance of these models was confirmed in all validation cohorts with satisfying predictive calibration and clinical application value. CONCLUSIONS: A CT radiomics-based model is promising to identify eosinophilic CRSwNP. This radiomics-based method may provide novel insights in solving other clinical concerns, such as guiding personalized treatment and predicting prognosis in patients with CRSwNP.

Stent pretreatment for internal carotid artery exposed to necrotic lesions in nasopharyngeal carcinoma.

BACKGROUND: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2-72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. METHODOLOGY: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. RESULTS: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. CONCLUSIONS: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

Exploratory and confirmatory factor analysis of the questionnaire on Palliative Care for Advanced Dementia (qPAD) using a large sample of staff from Australian residential aged care homes.

BACKGROUND: The Questionnaire on Palliative Care for Advanced Dementia (qPAD) is increasingly being used to assess residential aged care workers' knowledge and attitudes about palliative care for people with dementia. The qPAD developers performed an exploratory factor analysis and assessed the internal consistency using a small sample. AIM: The aim of this study was to further assess the structural validity of the qPAD using a large sample of qPAD responses from staff who work in residential aged care homes in Australia. METHODS: Data from 727 care staff who participated in an Australian dementia palliative care training project were used for exploratory factor analyses, assessment of internal consistency, and confirmatory factor analysis of the knowledge test and attitude scale components of the qPAD. RESULTS: The exploratory factor analysis of the knowledge test produced a four-factor solution. One item loaded weakly, and four items had cross-loadings. Factor labels for the knowledge test were difficult to define. Factor analysis of the attitude scale produced a three-factor structure with good internal consistency-Feeling valued and part of the care team (α = 0.88), Family and team engagement (α = 0.75) and Perceptions and beliefs (α = 0.83). Confirmatory factor analysis indicated improvements in model fit were needed for both the knowledge test and attitude scale. CONCLUSION: The findings of this factor analysis differed from the original study. The attitude scale produced a three-factor structure, but the knowledge test requires further development due to weak and cross-loadings of several items, inadequate internal consistency of factors and poor model fit.

Evaluation of IMproving Palliative care Education and Training Using Simulation in Dementia (IMPETUS-D) a staff simulation training intervention to improve palliative care of people with advanced dementia living in nursing homes: a cluster randomised controlled trial.

BACKGROUND: People with dementia have unique palliative and end-of-life needs. However, access to quality palliative and end-of-life care for people with dementia living in nursing homes is often suboptimal. There is a recognised need for nursing home staff training in dementia-specific palliative care to equip them with knowledge and skills to deliver high quality care. OBJECTIVE: The primary aim was to evaluate the effectiveness of a simulation training intervention (IMPETUS-D) aimed at nursing home staff on reducing unplanned transfers to hospital and/or deaths in hospital among residents living with dementia. DESIGN: Cluster randomised controlled trial of nursing homes with process evaluation conducted alongside. SUBJECTS & SETTING: One thousand three hundred four people with dementia living in 24 nursing homes (12 intervention/12 control) in three Australian cities, their families and direct care staff. METHODS: Randomisation was conducted at the level of the nursing home (cluster). The allocation sequence was generated by an independent statistician using a computer-generated allocation sequence. Staff from intervention nursing homes had access to the IMPETUS-D training intervention, and staff from control nursing homes had access to usual training opportunities. The predicted primary outcome measure was a 20% reduction in the proportion of people with dementia who had an unplanned transfer to hospital and/or death in hospital at 6-months follow-up in the intervention nursing homes compared to the control nursing homes. RESULTS: At 6-months follow-up, 128 (21.1%) people with dementia from the intervention group had an unplanned transfer or death in hospital compared to 132 (19.0%) residents from the control group; odds ratio 1.14 (95% CI, 0.82-1.59). There were suboptimal levels of staff participation in the training intervention and several barriers to participation identified. CONCLUSION: This study of a dementia-specific palliative care staff training intervention found no difference in the proportion of residents with dementia who had an unplanned hospital transfer. Implementation of the intervention was challenging and likely did not achieve adequate staff coverage to improve staff practice or resident outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12618002012257 . Registered 14 December 2018.

Probing the effects of dietary selenised glucose on the selenium concentration, quality, and antioxidant activity of eggs and production performances of laying hens.

Selenised glucose (SeGlu) is a newly invented organic selenium compound being synthesised through the selenisation reaction of glucose with NaHSe. We hypothesised that glucose could be used as a carrier for the stable low-valent organoselenium to enhance the selenium concentrations of eggs. To probe the effects of SeGlu on production performances of laying hens, egg selenium concentration, egg quality, and antioxidant indexes, 360 Hy-Line Brown laying hens were randomly assigned to three treatment groups fed with a basal diet alone or the diet supplemented with 5 or 10 mg/kg of Se from SeGlu. The results showed that SeGlu treatment not only enhanced (P < 0.001) the Se concentration in albumen and yolks, glutathione peroxidase activity, and total antioxidant capacity of eggs but also increased (P = 0.032) the Haugh unit of eggs being stored for 2 weeks, while the production performances and egg qualities of fresh eggs were not affected. Moreover, SeGlu supplementation linearly (P < 0.001) increased the scavenging ability of superoxide radicals in eggs. Briefly, SeGlu can enhance the selenium deposition and antioxidant activity of eggs, thereby meeting the nutritional requirement for Se-deficient humans.

Development of a Frailty Index from Routine Hospital Data in Perioperative and Critical Care.

BACKGROUND/OBJECTIVES: Frailty is common in surgical and intensive care unit (ICU) populations, yet it is not routinely measured. Frailty indices are able to quantify this condition across a range of health deficits. We aimed to develop a frailty index (FI) from routinely collected hospital data in a surgical and ICU population. DESIGN: Prospective observational single-center cohort study. SETTING: Tertiary referral metropolitan Australian hospital. PARTICIPANTS: A total of 336 individuals aged 65 and older undergoing surgery or aged 50 and older admitted to the ICU. MEASUREMENTS: Routine admission health data were used to derive an FI comprising 36 health deficits. We examined the FI correlation with existing frailty tools (Clinical Frailty Scale [CFS] and Edmonton Frail Scale [EFS]) and assessed its predictive ability for negative outcomes including 30-day mortality. RESULTS: Median FI was .17 (interquartile range [IQR]) = .10-.24) for ICU patients and .17 (IQR = .11-.25) for surgical patients; maximum FI was .58, and 25% (95% confidence interval [CI] = 10.4-29.6) of patients overall were diagnosed with frailty (FI score ≥.25). Correlation was strong between the FI and the EFS: ρ = .76 (95% CI = .70-.83) for ICU patients and .71 (95% CI = .64-.78) for surgical patients, and the CFS was .77 (95% CI = .70-.84) for ICU patients and .72 (95% CI = .65-.79) for surgical patients. The FI had good discriminative ability for prediction of 30-day mortality in ICU patients (multivariate odds ratio for each increase in FI of .1 = 2.04 [95% CI = 1.19-3.48]), comparable with the performance of the Acute Physiology and Chronic Health Evaluation III score (ICU patients) and the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity score (surgical patients). CONCLUSION: It is feasible to construct an FI from hospital admission data in a cohort of critically ill and surgical patients.

Persistent Barriers to Smoking Cessation Among Urban, Underserved Women: A Feasibility Study of Tailored Barriers Text Messages.

OBJECTIVES: Despite health risks for themselves and their children, urban underserved women smoke at high rates postpartum. The postpartum period is a stressful transition time that presents unique barriers to sustained cessation. There is limited extant evidence of efficacious psychosocial programs to maintain postpartum smoking cessation. METHODS: Guided by the Cognitive-Social Health Information Processing model, we explored the feasibility of TxT2Commit, a text-messaging intervention designed to prevent postpartum smoking relapse. Participants (n = 43) received supportive cessation-focused text messages for one month postpartum. Using a convergent mixed method design, surveys and interviews assessed changes in psychosocial factors and smoking status through a three month follow-up. RESULTS: Participants reported satisfaction with TxT2Commit, rating text messages as helpful, understandable, supportive, and not bothersome. However, a majority of women (n = 28, 65.1%) relapsed by three months. Participants who stayed smoke free (i.e., non-relapsers) reported significantly less temptation to smoke at one and three months postpartum compared to relapsers (ps < .01). While relapsers had significantly less temptation at one month compared to baseline, temptation increased by three months (p < .01). Consistent with the quantitative results, qualitative interviews identified informational and coping needs, with continued temptation throughout the three months. Non-relapsers were able to manage temptation and reported greater support. CONCLUSIONS FOR PRACTICE: TxT2Commit demonstrates preliminary feasibility and acceptability among urban, underserved postpartum women. However, most participants relapsed by three months postpartum. Additional research is needed to identify targeted messaging to best help women avoid temptation and bolster support to stay smoke free in this uniquely stressful period.

Accuracy of the Clinical Frailty Scale for perioperative frailty screening: a prospective observational study.

PURPOSE: Perioperative frailty increases postoperative complications, mortality, and new functional dependence. Despite this, routine perioperative frailty screening is not widespread. We aimed to assess the accuracy of the Clinical Frailty Scale (CFS) as a screening tool prior to anesthesia, and to determine which health domains are affected by frailty. METHODS: In a prospective, single-centre observational study, we enrolled 218 patients aged ≥ 65 yr undergoing elective and emergency surgery. The screening performance of the CFS was compared with the Edmonton Frail Scale, including the effect in individual frailty domains, and outcomes including discharge location and mortality. RESULTS: The median [interquartile range] age of the enrolled subjects was 74 [69-80] yr and 24% of the patients were frail. The CFS and Edmonton scales were highly correlated (Spearman correlation coefficient, 0.81; 95% confidence interval [CI], 0.77 to 0.86), and in substantial agreement (kappa coefficient, 0.76; 95% CI, 0.70 to 0.81), with an area under the receiver operating characteristic curve of 0.91 (95% CI, 0.86 to 0.94) indicating excellent discrimination for the CFS in predicting frailty status based on the Edmonton scale. Frail patients had higher 30-day mortality (odds ratio, 5.26; 95% CI, 1.28 to 21.62), and were less likely to be discharged home. Frail patients had poorer health throughout frailty domains, including functional dependence (42% of frail vs 4% of non-frail patients; P < 0.001), malnutrition (48% vs 19%, P < 0.001), and poor physical performance (47% vs 7%, P < 0.001). CONCLUSION: The CFS is a valid and accurate tool to screen for perioperative frailty, which encompasses the spectrum of health-related domains.

RéSUMé: OBJECTIF: La fragilité périopératoire augmente les complications postopératoires, la mortalité et une nouvelle dépendance fonctionnelle. Le dépistage de routine de la fragilité périopératoire n'est cependant pas une pratique répandue. Nous avions pour objectif d'évaluer la précision de l'échelle de mesure de fragilité CFS (pour Clinical Frailty Scale) comme outil de dépistage préanesthésique et de déterminer quels domaines de la santé étaient affectés par la fragilité. MéTHODE: Nous avons recruté 218 patients âgés de plus de 65 ans et subissant une chirurgie non urgente ou urgente dans notre étude observationnelle prospective et monocentrique. Les résultats du dépistage de la CFS ont été comparés à l'échelle de fragilité d'Edmonton (Edmonton Frail Scale), y compris en ce qui a trait à l'effet de la fragilité sur les domaines individuels de fragilité et aux résultats tels que la destination au congé et la mortalité. RéSULTATS: L'âge médian [écart interquartile] des patients recrutés était de 74 [69­80] ans et 24 % des patients étaient fragiles. Les échelles CFS et d'Edmonton avaient une forte corrélation (coefficient de corrélation de Spearman, 0,81; intervalle de confiance [IC] 95 %, 0,77 à 0,86) et étaient en accord substantiel (coefficient kappa, 0,76; IC 95 %, 0,70 à 0,81), avec une surface sous la courbe de fonction d'efficacité de l'observateur de 0,91 (IC 95 %, 0,86 à 0,94), indiquant une discrimination excellente de la CFS pour prédire l'état de fragilité fondé sur l'échelle d'Edmonton. Les patients fragiles souffraient d'une mortalité à 30 jours plus élevée (rapport de cotes, 5,26; IC 95 %, 1,28 à 21,62) et il était moins probable qu'ils reçoivent leur congé de l'hôpital à la maison. Les patients fragiles étaient en moins bonne santé dans tous les domaines de fragilité, notamment en dépendance fonctionnelle (42 % des patients fragiles vs 4 % des patients non fragiles; P < 0,001), en malnutrition (48 % vs 19 %, P < 0,001) et en mauvaise performance physique (47 % vs 7 %, P < 0,001). CONCLUSION: L'échelle CFS constitue un outil valable et précis pour dépister la fragilité périopératoire, qui englobe l'éventail des domaines liés à la santé.

Protocol for a prospective observational study to develop a frailty index for use in perioperative and critical care.

INTRODUCTION: Frailty is of increasing importance to perioperative and critical care medicine, as the proportion of older patients increases globally. Evidence continues to emerge of the considerable impact frailty has on adverse outcomes from both surgery and critical care, which has led to a proliferation of different frailty measurement tools in recent years. Despite this, there remains a lack of easily implemented, comprehensive frailty assessment tools specific to these complex populations. Development of a frailty index using routinely collected hospital data, able to leverage the automated aspects of an electronic medical record, would aid risk stratification and benefit clinicians and patients alike. METHODS AND ANALYSIS: This is a prospective observational study. 150 intensive care unit (ICU) patients aged ≥50 years and 200 surgical patients aged ≥65 years will be enrolled. The primary objective is to develop a frailty index. Secondary objectives include assessing its ability to predict in-hospital mortality and/or discharge to a new non-home location; the performance of the frailty index in predicting postoperative and ICU complications, as well as health-related quality of life at 6 months; to compare the performance of the frailty index against existing frailty measurement and risk stratification tools; and to assess its modification by patients' health assets. ETHICS AND DISSEMINATION: This study has been approved by the Melbourne Health Human Research Ethics Committee(20 January 2017, HREC/16/MH/321). Dissemination will be via international and national anaesthetic and critical care conferences, and publication in the peer-reviewed literature.

Characterization and proteomic profiling of pancreatic cancer-derived serum exosomes.

Pancreatic cancer (PC) is one of the most lethal cancers known worldwide, and its prognosis is poor in most patients. Exosomes are nanosized extracellular vesicles, which are released from various cell types. They are involved in cellular communication. The diagnosis and treatment of PC were improved substantially with exosomes. In this study, we isolated PC-derived exosomes and investigated their proteomic profile. Then, we conducted bioinformatic analysis on proteomic data. Differential ultracentrifugation was performed to isolate exosomes from human serum samples and four PC cell lines. Transmission electron microscopy and Western blot analysis were used to characterize the isolated exosomes. Liquid chromatography coupled with tandem mass spectrometry was conducted to identify the proteome of serum exosomes. Proteomic analysis demonstrated that all the serum exosomes were derived from three cohorts of human subjects; these serum exosomes contained a total of 655 proteins, out of which 315 proteins overlapped with ExoCarta database. Gene oncology and kyoto encyclopedia of genes and genomes analyses provided the functional annotation of the proteome. Interestingly, 18 or 14 proteins were upregulated and 11 or 14 proteins were downregulated in serum exosomes derived from patients with PC as compared with in serum exosomes derived from healthy volunteers or from pancreatitis patients respectively. Annexin A11, a calcium-dependent phospholipid-binding protein, was expressed in a PC cell line (CFPAC-1)-derived exosomes and in tumor tissues of patients with PC, respectively. Our data provided a basic foundation for further studies on the protein composition of PC-derived exosomes and its involvement in PC biology.

Long-term outcomes and quality of life following ligation of the intersphincteric fistula tract for high transsphincteric fistulas.

AIM: Published outcomes following ligation of the intersphincteric fistula tract (LIFT) for high transsphincteric fistulas (HTFs) are equivocal probably because most trials are small and comprise mixed patient populations. The aim of this study was to highlight the long-term efficacy of LIFT for HTFs in a large homogeneous sample and to determine the risk factors that contribute to non-healing resulting in failure and recurrence. METHOD: A retrospective study was performed which assessed patients with HTFs treated by LIFT without prior loose setons from September 2012 to December 2017. Continence function was evaluated by the Wexner incontinence scale and anal manometry. Quality of life was assessed by using the faecal incontinence quality of life (FIQL) scale with four domains: lifestyle, coping, depression and embarrassment. RESULTS: Seventy patients with HTFs underwent 71 LIFT procedures. The primary healing rate was 81.7% with a median follow-up duration of 16.5 (range 4.5-68) months. The healing rates of mature and immature fistulas were 83.7% and 77.3%, respectively. Two patients suffered failure with an unhealed intersphincteric wound. Recurrence occurred in 11 patients. Incontinence of flatus, present in four patients before surgery, improved postoperatively. Two patients undergoing LIFT combined with fistulotomy complained of flatus incontinence after surgery. No significant differences between preoperative and postoperative Wexner score, maximum resting pressure and maximum squeeze pressure were detected. The FIQL was improved in lifestyle, coping and depression. No risk factor for non-healing was found. CONCLUSION: LIFT has a promising long-term outcome for HTFs, with negligible impairment on continence and improved quality of life.

Using graphical representations to enhance the quality-of-care for colorectal cancer patients.

The study was to enhance adherence to quality-of-care guidelines for colorectal cancer (CRC) patients through plotting graphical representations. Rasch analysis was performed to examine the unidimensional measurement of the 13 core indicators. An author-made Excel module was applied to plot the so-called Wright map and KIDMAP in education field to report physicians' adherence to the quality-of-life guidelines. We found that the scale of the quality-of-care guidelines for patients with colon cancer is unidimensional. A total of 15 (3.8%) and 14 (3.5%) persons' response patterns (i.e., Outfit MNSQs >2.0 and 4.0, respectively) are aberrantly dispersed from the majority of sample according to their estimated parameters of persons and indicators. It can be used for investigating the root cause of the 1ow measures and/or the most unexpected aberrant pattern of responses using Rasch analysis once any one indicator of unexpectedly aberrant treatment (p < .05) presents. The Rasch model can deal with these binary and/or missing data frequently seen in clinical settings. We confirm this computer module can contribute to ensuring that hospitals adhere to the treatment guidelines for patients with colon cancer.

Nucleotide excision repair is a potential therapeutic target in multiple myeloma.

Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents. Next, using small RNA interference, stable knockdown and overexpression, and small-molecule inhibitors targeting xeroderma pigmentosum complementation group B (XPB), the DNA helicase encoded by ERCC3, we demonstrate that NER inhibition significantly increases sensitivity and overcomes resistance to alkylating agents in MM. Moreover, inhibiting XPB leads to the dual inhibition of NER and transcription and is particularly efficient in myeloma cells. Altogether, we show that NER impacts alkylating agents sensitivity in myeloma cells and identify ERCC3 as a potential therapeutic target in MM.

[Initial osteoblast functions on a type of near ß-type titanium alloys surfaces modified by the double glow plasma nitriding technology].

Objective: To evaluate the adhesion, proliferation, alkaline phosphatase (ALP) activity and the expression of osteogenesis-related genes and osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) of osteoblast-like cells on a type of near ß-type titanium alloys (Ti-5Zr-3Sn-5Mo-15Nb, TLM) surfaces modified by the double glow plasma nitriding technology, and to investigate the effect of the modified surfaces on the initial functions of osteoblast-like cells. Methods: The surfaces of TLM were modified by the double glow plasma nitriding technology. TLM surfaces without modification were used as control. Cell morphology was observed with scanning electron microscopy (SEM). Methyl thiazolyl tetrazolium (MTT) method was used to measure cell proliferation. Cell ALP activity was evaluated by using reagent kits. The mRNA expression of Runt-related transcription factor-2 (RUNX2), typeⅠcollagen alpha 1 chain (COLⅠ α1) and OPG/RANKL were examined by quantitative real-time PCR(qRT-PCR). Results: Four hour following cell alture, cells on modified surfaces extend filopodia and intercellular junction was tight. Three days later, cell proliferation (0.277±0.007) was significantly higher than that in control group (0.249±0.004) (P<0.01). After two weeks, ALP activity on TLM modified layer (173.6±1.89) was significantly higher than that on unmodified TLM (162.6±2.4) (P<0.01). The mRNA expression of osteoblast marker RUNX2, COLⅠα1 were stronger than that in control group (P<0.05). The expression of OPG mRNA was higher than that in control group (P<0.01), and RANKL mRNA expression was significantly lower than that in control group (P<0.05). Conclusions: The TLM surface modified by the double glow plasma nitriding technology has a positive effect on osteoblasts initial adhesion, proliferation and differentiation, and it can also improve expression of OPG mRNA and has an inhibitory effect on RANKL mRNA expression of osteoblasts.

[One case of 28+ weeks pregnancy with esthesioneuroblastoma].

A 21 years old female patient was admitted to hospital for "menolipsis of 28 weeks, discovery of nasal neoplasm for 2 months, headache for 10 days" .check: The left nasal cavity was filled with a red neoplasm extending to the edge of the nasal vestibule , with incrustation on its surface and easy haemorrhage when touched.Sinus CT: the left side of the nasal vestibule, nasal meatus and the whole sets of sinuses were full of soft tissue density with nasal bone absorption, malignant diseases not excluded.MRI: The left side of the nasal vestibule, nasal passages, cribriform roof and frontal sinus were filled with equal T1 and long T2 signal, with obvious tortuous signal of voids of vessel , partially extending into the left orbit, and accompanied with obstructive sinusitis.Postoperative pathologic and immunohistochemical results diagnosed as esthesioneuroblastoma.